Quinn L M, Herr A, McGarry T J, Richardson H
Peter MacCallum Cancer Institute, Trescowthick Research Laboratories, Locked Bag 1, Melbourne, Victoria 8006, Australia.
Genes Dev. 2001 Oct 15;15(20):2741-54. doi: 10.1101/gad.916201.
We have identified a Drosophila homolog of the DNA replication initiation inhibitor Geminin (Dm geminin) and show that it has all of the properties of Xenopus and human Geminin. During Drosophila development, Dm Geminin is present in cycling cells; protein accumulates during S phase and is degraded at the metaphase to anaphase transition. Overexpression of Dm geminin in embryos inhibits DNA replication, but cells enter mitosis arresting in metaphase, as in dup (cdt1) mutants, and undergo apoptosis. Overexpression of Dm Geminin also induces ectopic neural differentiation. Dm geminin mutant embryos exhibit anaphase defects at cycle 16 and increased numbers of S phase cells later in embryogenesis. In a partially female-sterile Dm geminin mutant, excessive DNA amplification in the ovarian follicle cells is observed. Our data suggest roles for Dm Geminin in limiting DNA replication, in anaphase and in neural differentiation.
我们鉴定出了DNA复制起始抑制剂Geminin的果蝇同源物(Dm geminin),并表明它具有非洲爪蟾和人类Geminin的所有特性。在果蝇发育过程中,Dm Geminin存在于循环细胞中;蛋白质在S期积累,并在中期到后期转换时降解。胚胎中Dm geminin的过表达抑制DNA复制,但细胞进入有丝分裂并停滞在中期,就像在dup(cdt1)突变体中一样,然后发生凋亡。Dm Geminin的过表达还会诱导异位神经分化。Dm geminin突变胚胎在第16个细胞周期表现出后期缺陷,并且在胚胎发育后期S期细胞数量增加。在一个部分雌性不育的Dm geminin突变体中,观察到卵巢滤泡细胞中存在过度的DNA扩增。我们的数据表明Dm Geminin在限制DNA复制、后期和神经分化中发挥作用。